Reinforcement of Interfacial Adhesion of a Coated Polymer Layer on a Cobalt–Chromium Surface for Drug-Eluting Stents

Bedair, Tarek M.,Cho, Youngjin,Kim, Tae Jung,Kim, Young Dong,Park, Bang Ju,Joung, Yoon Ki,Han, Dong Keun American Chemical Society 2014 Langmuir Vol.30 No.27

<P>During the balloon expansion of several commercially available drug-eluting stents, various types of defects in the polymer layer have been observed. The aim of this study is to prevent these defects by increasing the interfacial adhesion between the metal substrate and the drug-in-polymer matrix using poly(caprolactone) (PCL) brushes onto a cobalt–chromium (Co–Cr or CC) alloy surface. The chemical modification of the Co–Cr surface was accomplished by grafting ricinoleic acid (RA) onto the metal substrate followed by surface-initiated ring opening polymerization of ε-caprolactone. The unmodified, RA-grafted (CC-RA), and PCL-grafted Co–Cr substrates (CC-RA-PCL3D and CC-RA-PCL6D) were characterized by various surface analyses. Poly(<SMALL>d</SMALL>,<SMALL>l</SMALL>-lactide) containing sirolimus was spray coated onto the unmodified and modified substrates. The adhesion property of the polymer coating on the PCL-grafted surfaces was improved compared to those of other samples. Among all of the drug-in-polymer coated samples, both CC-RA-PCL3D and CC-RA-PCL6D exhibited a stabilized drug release profile over 49 days. It was also revealed that CC-RA-PCL6D showed the slowest drug release of all the samples. On the basis of these results, the proposed nanocoupling method has shown not only improved adhesion of the drug-in-polymer matrix to the Co–Cr substrate but also controlled drug release.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2014/langd5.2014.30.issue-27/la501990p/production/images/medium/la-2014-01990p_0009.gif'></P>

Coating defects in polymer-coated drug-eluting stents

Bedair, Tarek M.,Cho, Youngjin,Park, Bang Ju,Joung, Yoon Ki,Han, Dong Keun Techno-Press 2014 Biomaterials and Biomechanics in Bioengineering Vol.1 No.3

Vascular stenting has a great attention as a treatment for coronary arteries diseases as compared with percutaneous balloon angioplasty. In-stent restenosis and thrombosis are side effects resulting from using bare metal stent (BMS). Employing platelet therapy allowed to reduce the rate of thrombosis, however, the rate of restenosis remains a major problem. In 2002, drug-eluting stents (DESs) were introduced as an effort to reduce the restenosis. The commercially available DESs continue to suffer from coating defects that might lead to a series of adverse effects. Most importantly, multiple concerns remain regarding the polymer coating integrity on metal surfaces or the relation of polymer irregularities to longterm adverse events.

Dual-Layer Coated Drug-Eluting Stents with Improved Degradation Morphology and Controlled Drug Release

Bedair, Tarek M.,Park, Wooram,Park, Bang-Ju,Moon, Myoung-Woon,Lee, Kwang-Ryeol,Joung, Yoon Ki,Han, Dong Keun The Polymer Society of Korea 2018 Macromolecular Research Vol.26 No.7

Drug-eluting stents (DESs) are used to treat cardiovascular diseases such as atherosclerosis. The anti-proliferative drug released from the DES suppress the proliferation of smooth muscle cells and reduced in-stent restenosis. However, a burst release of the drug in the early stages and degradation morphology of the polymer coating represent major disadvantages, which might increase the incidence of in-stent restenosis and/or thrombosis under in vivo clinical studies. To solve these problems, in this study, a double-layer coating system composed of poly(lactide) (PLLA) bottom layer and poly(lactide-co-glycolide) (PLGA) top layer are used for the fabrication of DES. PLLA bottom layer was firstly coated on the metal surface followed by oxygen ion beam treatment. It was found that increasing the ion beam exposure time, increased the roughness of PLLA surface with a nanoscale pocket (or hole)-like structure. The top layer coating represented a mixture of PLGA and paclitaxel (PTX) with 5, 10, and 20% PTX contents. The coating was performed through ultrasonic spray technique, and the morphology showed not only a smooth and uniform surface but also no irregularities were observed at zero day. The drug release and degradation morphology for single-layer (PLGA/PTX) and double-layer (PLLA/PLGA/PTX) coatings were compared. The drug release from the double-layer stainless steel (SS) group showed a slower and controlled drug release for all PTX content samples as compared to single-layer SS group. Moreover, the degradation morphology of double-layer SS group presented a smoother and uniform surface after 12 weeks of degradation under physiological conditions. Therefore, an oxygen ion beam technique with double-layer coating system could effectively control the drug release, i.e., prevent initial burst drug release, and improve the degradation morphology of biodegradable polymer-based DESs.

Covalent immobilization of fibroblast-derived matrix on metallic stent for expeditious re-endothelialization

Tarek M. Bedair,민일재,박우람,박방주,정윤기,한동근 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.70 No.-

Here, we demonstrate afibroblast-derived extracellular matrix (FDM) immobilized cobalt-chromium(Co–Cr) alloy surface to accelerate re-endothelialization. The surface characterization results showedthat FDM molecules with their protein components such as collagen I,fibronectin, and laminin, werecovalently grafted to Co–Cr surface. The in vitro cells experiments exhibited the superiority of the FDMimmobilizedsurface to capture and proliferate of endothelial progenitor and human umbilical cord veinendothelial cells than control Co–Cr alloy. These results suggested that the immobilization of FDM on thestent surface by this facile procedure could be an efficient and promising strategy to get expeditious reendothelialization.

Persulfated flavonoids accelerated re-endothelialization and improved blood compatibility for vascular medical implants

Bedair, Tarek M.,Bedair, Hanan M.,Ko, Kyoung-Won,Park, Wooram,Joung, Yoon Ki,Han, Dong Keun Elsevier 2019 Colloids and Surfaces B Vol.181 No.-

<P><B>Abstract</B></P> <P>Drug-eluting stents (DESs) have been used for the treatment of cardiovascular diseases including stenosis. However, in-stent restenosis, thrombosis, and delayed re-endothelialization represent challenges for their clinical applications. Here, we demonstrate a novel work to overcome these limitations through surface modification technology. The cobalt-chromium (Co-Cr) surface was modified with antioxidants such as gallic acid (GA) and rutin (Ru) and the corresponding persulfates derivatives (<I>i.e</I>., GAS, and RuS) through a simple conjugation procedure. Various analyses tools such as ATR-FTIR, XPS, water contact angle, SEM, and AFM characterized the functionalized surface. The surface characterization confirmed that the antioxidant and the additional persulfates were successfully bonded to the Co-Cr surface. The results of <I>in vitro</I> endothelial cells proved that the persulfates derivatives showed the highest tendency to get rapid re-endothelialization especially RuS. In addition, it showed inhibition to smooth muscle cells (SMCs) as compared to control Co-Cr substrate. The persulfates modified substrates reduced the amount of adsorbed fibrinogen and albumin with higher stability to fetal bovine serum. Moreover, platelet study also demonstrated that Ru and RuS presented lower platelet adhesion with round shape morphology, whereas the control Co-Cr adhere and activate many platelets with pseudopodium morphology. Moreover, these modification processes did not cause any inflammatory responses. In conclusion, it is believed that the persulfates flavonoids have a great potential in the field of drug-eluting stents and blood contacting medical implants to improve blood compatibility, suppress SMCs, and get rapid re-endothelialization.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Antioxidants/persulfates were successfully and covalently grafted on Co-Cr substrate. </LI> <LI> The persulfated-engineered substrates present rapid re-endothelialization. </LI> <LI> Gallic acid persulfate and rutin persulfate exhibit low protein adsorption. </LI> <LI> Rutin and rutin persulfate demonstrate reduced platelet adhesion and activation. </LI> <LI> These modification processes does not cause any inflammatory responses. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Covalent immobilization of fibroblast-derived matrix on metallic stent for expeditious re-endothelialization

Bedair, Tarek M.,Min, Il Jae,Park, Wooram,Park, Bang Ju,Joung, Yoon Ki,Han, Dong Keun Elsevier 2019 Journal of industrial and engineering chemistry Vol.70 No.-

<P><B>Abstract</B></P> <P>Here, we demonstrate a fibroblast-derived extracellular matrix (FDM) immobilized cobalt-chromium (Co–Cr) alloy surface to accelerate re-endothelialization. The surface characterization results showed that FDM molecules with their protein components such as collagen I, fibronectin, and laminin, were covalently grafted to Co–Cr surface. The <I>in vitro</I> cells experiments exhibited the superiority of the FDM-immobilized surface to capture and proliferate of endothelial progenitor and human umbilical cord vein endothelial cells than control Co–Cr alloy. These results suggested that the immobilization of FDM on the stent surface by this facile procedure could be an efficient and promising strategy to get expeditious re-endothelialization.</P> <P><B>Graphical abstract</B></P> <P> <B>FDM capturing technique for expeditious re-endothelialization:</B> </P> <P>After stent deployment, (1) endothelial cells were denuded or damaged, (2) covalently FDM proteins grafted on metal stent were able to capture the circulating endothelial progenitor cells (EPCs), and (3) the captured EPCs were transformed to normal (healthy) endothelial cells to form a normal endothelial layer for expeditious re-endothelialization.</P> <P>[DISPLAY OMISSION]</P>

Coating defects in polymer-coated drug-eluting stents

Bedair, Tarek M.,Cho, Youngjin,Park, Bang Ju,Joung, Yoon Ki,Han, Dong Keun Techno-Press 2014 Biomaterials and biomedical engineering Vol.1 No.3

Vascular stenting has a great attention as a treatment for coronary arteries diseases as compared with percutaneous balloon angioplasty. In-stent restenosis and thrombosis are side effects resulting from using bare metal stent (BMS). Employing platelet therapy allowed to reduce the rate of thrombosis, however, the rate of restenosis remains a major problem. In 2002, drug-eluting stents (DESs) were introduced as an effort to reduce the restenosis. The commercially available DESs continue to suffer from coating defects that might lead to a series of adverse effects. Most importantly, multiple concerns remain regarding the polymer coating integrity on metal surfaces or the relation of polymer irregularities to longterm adverse events.

Improved mechanical and biological properties of biodegradable thinner poly(L-lactic acid) tubes by bi-directional drawing

Ginam Han,Tarek M. Bedair,Dae Hwan Kim,Keun-Hong Park,Wooram Park,Dong Keun Han 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.90 No.-

Fully biodegradable polymer stents still suffer from weak mechanical properties and thick stent struts,which could induce thrombosis under in vivo clinical applications. To address these problems, wefabricated a thinner poly(L-lactic acid) (PLLA) tube with improved mechanical properties through athermal drawing process and characterized the tubes using several analytical tools. The mechanicalproperties of the tubes showed that the optimized conditions for the axial drawing were at 65 C (A65)and 95 C (A95), and those for the radial drawing process were also at 65 C (R65) and 95 C (R95). The bidirectionaldrawing process (A65/R95), performed at 65 C for axial and then at 95 C for radial drawings,demonstrated an excellent way to reduce the thickness of the tubes while reinforcing the mechanicalproperties. In addition, it reduced the amount of adsorbedfibrinogen and increased the albumin/fibrinogen ratio. Moreover, the platelet adhesion exhibited lower number and activity with completelyround morphology. It also promoted the adhesion and proliferation of endothelial cells with stretchedmorphology and a significant increase offilopodial outgrowth. From these results, it can be seen that acombination of the axial and radial processes may be a promising strategy for improving thephysicochemical, mechanical, and biological properties of PLLA tubes to be used for the fabrication offully biodegradable polymeric stents.

Effect of various shaped magnesium hydroxide particles on mechanical and biological properties of poly(lactic-co-glycolic acid) composites

장혜정,박성빈,Tarek M. Bedair,오민규,안동준,박우람,정윤기,한동근 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.59 No.-

Five different shapes of magnesium hydroxide (Mg(OH)2) particles (Plate-S, Plate-N, Disk, Whisker, and Fiber) were synthesized and added to biopolymer (i.e., Poly(lactic-co-glycolic acid) (PLGA)) composite to improve their mechanical and biological properties. The PLGA composite films including Mg(OH)2 particles were prepared by a solvent casting method. Their mechanical and biological properties were compared according to the composites containing different shapes of Mg(OH)2 particles. Among them, the fiber shape of Mg(OH)2 provided the highest mechanical strength, and anti-inflammation and anti-bacterial activity to PLGA films among other forms. This study demonstrated a new strategy for the design of biomaterials by controlling the form of inorganic additives.

Biodegradable sheath-core biphasic monofilament braided stent for bio-functional treatment of esophageal strictures

한철민,이유진,최슬기,Tarek M. Bedair,이영재,박우람,한동근,손준식,정윤기 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.67 No.-

In this study, a polydioxanone (PDO) and poly(L-lactic acid) (PLLA) sheath-core biphasic monofilament was designed to develop an esophageal stent with improved mechanical properties and controlled biodegradability. The radial force of PDO/PLLA sheath-core stent was 10.24 N, while that of PDO stent was 5.64 N. Deteriorations of tensile strength, elastic modulus and elongation during degradation test were also delayed on PDO/PLLA group. Hyaluronic acid–dopamine conjugate and BaSO4/PDO conjugate coating layers provided improved tissue adhesion strength and reasonable X-ray contrast, respectively. Taken all together, the sheath-core filaments with tissue adhesive and radiopaque properties will be useful in designing esophageal stents.